While the first-line setting of non–small cell lung cancer (NSCLC) drastically changed when the PD-1 inhibitor pembrolizumab (Keytruda) was granted FDA approval in October 2016 for metastatic patients, an ongoing trial could potentially give early-stage patients an immunotherapy option, as well.

The phase III ANVIL study is randomizing patients with stage IB to IIIA NSCLC to receive adjuvant therapy with nivolumab (Opdivo) following surgical resection and chemotherapy (NCT02595944). Investigators hope that the addition of immunotherapy will kill additional tumor cells still present even after these traditional treatment methods. Aside from this trial, researchers are also exploring PD-1/CTLA-4 combinations as first-line treatment in an effort to hit multiple immune targets.

“We know that these areas of checkpoint inhibition are like brakes on a car; there may be more than 1 brake,” says Daniel Costin, MD. “If we can block these areas at multiple sites, we can have much more effective therapy.”

During the 2017 OncLive® State of the Science Summit on Advanced Non–Small Cell Lung Cancer, Costin, who specializes in hematology and oncology at White Plains Hospital, lectured on checkpoint inhibition in the first- and second-line settings for patients with NSCLC. In an interview during the meeting, he shared insight on understanding the deeper biology of the immune system, the emerging research with immunotherapy, and the importance of managing associated adverse events.

OncLive: What is the current state of immunotherapy in lung cancer?

Costin: This is a very interesting time in cancer therapy because we now have introduction of immunotherapy into the treatment of our patients with very different cancers. Traditionally, patients who had locally advanced NSCLC were treated with chemotherapy. About 7 years ago, we had the first patients being offered checkpoint inhibition and we began to see that this was a major change and a breakthrough in the management of these patients.

In terms of checkpoint inhibition, the concept is to try to allow our own immune system to get rid of the cancer. Cancer cells can avoid our immune system through various checkpoints; they act almost like brakes. If we can somehow dislodge or unlock those brakes, we allow our own immune system to start attacking the cancer cells and to eradicate them.

The various new treatments that are now available are aimed at focusing on these particular areas where the brakes to our immune system exist. The 2 drugs that are now most commonly used in the forefront are the PD-1 antibodies nivolumab and pembrolizumab. There have been numerous important clinical trials that have brought these drugs to the forefront.

In addition, we also understand that checkpoint inhibition works in different areas of our immune system. New drugs that are aimed at antagonizing or blocking PD-L1 are now also being offered to patients and getting FDA approval. The future will likely hold combinations of checkpoint inhibition.

Over the last several years, the initial approach to using immunotherapy with checkpoint inhibition has primarily been in individuals with advanced NSCLC and disease that has progressed on primary chemotherapy. A lot of our initial clinical studies have shown that in these patients, when you compare immunotherapy with standard second-line chemotherapy, there were very dramatic responses and benefits. Many patients have shown prolonged survival and continue to show disease-free states at 12 months, 18 months, and even 24 months after starting therapy. We are seeing not just responses and prolonged progression-free survival, but improved overall survival and quality of life, as well.

What about the first-line setting?

For second-line therapy, immunotherapy has become very much a standard of care. An interesting, important clinical question that exists now is, can we start to introduce immunotherapy as first-line therapy and should we be thinking about immunotherapy in patients with early-stage lung cancer?

Traditionally, those patients are treated with surgery followed by chemotherapy, but many of those patients still recur and will potentially die from their cancer. If immunotherapy works so well, can we start thinking about it in that setting? There are important studies addressing that. For nivolumab, there is a national study called ANVIL that is looking at men and women with early-stage lung cancer who have standard surgery followed by chemotherapy, if appropriate, followed by randomization with nivolumab or placebo.

That is a very important question because even in our patients with early lung cancer, we are still finding many patients with recurrences who are still susceptible to dying of their cancer.